       Document 0446
 DOCN  M9640446
 TI    In vivo role of IL-6 on the viral load and on immunological
       abnormalities of HIV-infected patients.
 DT    9604
 AU    Marfaing-Koka A; Aubin JT; Grangeot-Keros L; Portier A; Benattar C;
       Merrien D; Agut H; Aucouturier P; Autran B; Wijdenes J; et al; INSERM
       U131, Institut Paris-Sud sur les Cytokines, Clamart,; France.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Jan 1;11(1):59-68.
       Unique Identifier : AIDSLINE MED/96130048
 AB    In vitro experiments have suggested that interleukin (IL)-6 may
       contribute to human immunodeficiency virus (HIV) burden and to
       immunological abnormalities in HIV-infected patients. We had the
       opportunity to directly address this question in vivo through the
       virological and immunological monitoring of HIV-infected patients
       treated with an anti-IL-6 monoclonal antibody (mAb) for a lymphoma (ANRS
       018 trial). Sixteen courses of anti-IL-6 mAb administration, performed
       in 11 patients, were studied. All patients were at a late stage of HIV
       infection. The HIV load and the immunological status were determined at
       the initiation of each course and at its end, 21 days later. The mAb
       induced no significant change of HIV load, as evaluated by p24
       antigenemia, plasma viremia, and quantification of circulating HIV RNA
       by reverse transcriptase-polymerase chain reaction and branched DNA
       techniques. The anti-IL-6 mAb also did not affect CD4+, CD8+, and CD19+
       circulating cell counts, nor the serum concentrations of sIL-2R and of
       sCD8. In contrast, the mAb completely abrogated acute-phase reaction, as
       demonstrated by the normalization of C-reactive protein and fibrinogen
       circulating levels (p = 0.013 and p = 0.008, respectively). It increased
       serum albumin concentration. The latter effect was restricted to
       patients with a spontaneously low albuminemia (p = 0.01). It decreased
       B-lymphocyte hyperactivity, as reflected by decreased IgG and IgA serum
       levels (p = 0.008 and p < 0.001, respectively), and by a decreased
       production of IgG in vitro (p = 0.017). In contrast, the IgM
       hyperproduction was not affected by the mAb. Therefore, increased IL-6
       production in HIV-infected patients at a late stage of the infection may
       not stimulate HIV replication in vivo, but it may represent a key
       mechanism contributing to the metabolic and immunological dysbalance of
       the disease.
 DE    Acute-Phase Proteins/ANALYSIS  Acute-Phase
       Reaction/ETIOLOGY/PHYSIOPATHOLOGY/THERAPY  Antibodies,
       Monoclonal/ADMINISTRATION & DOSAGE/THERAPEUTIC USE  Antigens, CD8/BLOOD
       B-Lymphocytes/IMMUNOLOGY  Human  HIV Core Protein p24/ANALYSIS  HIV
       Infections/COMPLICATIONS/*IMMUNOLOGY/VIROLOGY  HIV-1/*PHYSIOLOGY
       IgA/ANALYSIS  IgG/ANALYSIS  Immunophenotyping  Infusions, Intravenous
       Interleukin-6/IMMUNOLOGY/*PHYSIOLOGY  Lymphocyte Count  Lymphoma,
       AIDS-Related/PHYSIOPATHOLOGY/THERAPY  Lymphoma,
       High-Grade/PHYSIOPATHOLOGY/THERAPY  Receptors, Interleukin-2/ANALYSIS
       RNA, Viral/ANALYSIS  Support, Non-U.S. Gov't  Viremia/PHYSIOPATHOLOGY
       *Virus Replication  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

